Published online October 22, 2007
doi:10.1084/jem.20071261
The Journal of Experimental Medicine, Vol. 204, No. 11, 2505-2512
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Maness et al.
AIDS virus–specific CD8+ T lymphocytes against an immunodominant cryptic epitope select for viral escape
Nicholas J. Maness1,
Laura E. Valentine1,
Gemma E. May1,
Jason Reed1,
Shari M. Piaskowski2,
Taeko Soma1,
Jessica Furlott1,
Eva G. Rakasz1,
Thomas C. Friedrich1,
David A. Price3,
Emma Gostick3,
Austin L. Hughes4,
John Sidney5,
Alessandro Sette5,
Nancy A. Wilson1, and
David I. Watkins1,2
1 Wisconsin National Primate Research Center, University of Wisconsin-Madison, Madison, WI 53711
2 Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI 53706
3 Weatherall Institute for Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, UK
4 Department of Biological Sciences, University of South Carolina, Columbia, SC 29208
5 The La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037
CORRESPONDENCE David I. Watkins: watkins{at}primate.wisc.edu
Cryptic major histocompatibility complex class I epitopes have been detected in several pathogens, but their importance in the immune response to AIDS viruses remains unknown. Here, we show that Mamu-B*17+ simian immunodeficiency virus (SIV)mac239-infected rhesus macaques that spontaneously controlled viral replication consistently made strong CD8+ T lymphocyte (CD8-TL) responses against a cryptic epitope, RHLAFKCLW (cRW9). Importantly, cRW9-specific CD8-TL selected for viral variation in vivo and effectively suppressed SIV replication in vitro, suggesting that they might play a key role in the SIV-specific response. The discovery of an immunodominant CD8-TL response in elite controller macaques against a cryptic epitope suggests that the AIDS virus–specific cellular immune response is likely far more complex than is generally assumed.

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